Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the release of histamine, a major mast cell mediator of conjunctival type I reactions, and the production of a prostanoid, prostacyclin (prostaglandin I2, PGI2), was examined in a guinea pig model of allergic conjunctivitis. Guinea pigs were sensitized topically and challenged by repeated conjunctival instillation of fluoresceinyl ovalbumin. Histamine and 6-keto-PGF1 alpha, the stable product of the spontaneous degradation of PGI2, were measured in tears by radioimmunoassays. Clinical type I reactions and tear histamine appeared by 8 days and increased up to 22 days during the initial sensitization, with notable variations between animals. The kinetics of histamine and 6-keto-PGF1 alpha release in tears were examined over a 24-hr period after the antigen challenge. Histamine release was maximal during the first 10 min and returned to baseline values by 1 hr in all instances. The 6-keto-PGF1 alpha release also peaked during the first 10 min but continued for an extended period. The ratio of tear 6-keto-PGF1 alpha to histamine increased more than 16-fold over the 2 hr after antigen challenge. Late-phase reactions with second peaks of histamine or 6-keto-PGF1 alpha in the tears were observed in two different guinea pigs 4-8 hr after antigen challenge. Histamine applied to the eyes of naive guinea pigs also induced the release of 6-keto-PGF1 alpha in tears. Histamine appeared to act as a primary mediator, stimulating the secondary production and release of PGI2 by constitutive (eg, vascular) and possibly infiltrating inflammatory cells during an allergic conjunctival reaction.
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PMID:Histamine and prostacyclin. Primary and secondary release in allergic conjunctivitis. 171 64

Evidence implicating synovial mast cells in the initiation and perpetuation of arthritis has increased. We have developed a method of joint lavage to monitor dynamic intraarticular events in the intact animal. Lavage was done before and after immunologic (passive sensitization followed by intravenous specific antigen or intraarticular anti-rat immunoglobulin E [IgE] heteroantiserum) and nonimmunologic (intraarticular calcium ionophore A-23187; phorbol 12-myristate, 13-acetate; and compound 48/80) synovial mast cell activation. To quantify and analyze synovial mast cell mediator release kinetics in situ, we measured lavage fluid histamine. With all activation protocols except A-23187, histamine release was evident within 5 minutes after introduction of the stimulus. The quantitative and chronological similarities between immunologically induced and compound 48/80-induced synovial mast cell histamine release kinetics suggested that connective tissue type mast cells are an important source of inflammatory mediators in rat joints. We also measured joint lavage fluid histamine levels in rats immunized with an active sensitization protocol. Histamine levels were determined by the autoanalyzer method and were confirmed by using a commercially available radioimmunoassay that uses a monoclonal antibody against acetylated histamine. We found that in many of these animals, at the peak of the serum IgE response, joint lavage fluid histamine levels were very high even before challenge with specific antigen, and that this increase was not due to diffusion into the joint of abnormally elevated plasma histamine. These data suggested that synovial mast cells are preferentially activated in states of high serum IgE immune responses. We have used a simple, inexpensive, rapid lavage technique to generate the first data on histamine release kinetics after selective synovial mast cell activation in the intact animal. The technique can be adapted for investigation of release kinetics of a variety of other substances from activated synovial cells and can be used in other arthritis models.
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PMID:A lavage method for dynamic intraarticular monitoring of animal joints in situ: quantification and release kinetics of histamine after selective synovial mast cell activation by diverse secretagogues. 171 21

Endogenous and exogenous free radical scavengers significantly decrease mast cell histamine release induced by coincubation with resting, activated platelets or with platelet-derived supernatant. Histamine and pyridylethylamine dose-dependently enhance platelet aggregation; the effect is potentiated by ranitidine and blocked by mepyramine. Histamine increases also cytosolic calcium concentration in platelets stimulated with thrombin, and binding sites for [3H]-mepyramine are present on platelet membranes.
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PMID:Definition of platelet-derived histamine-releasing factor and histaminergic receptors modulating platelet aggregation. 171 91

Various stressful stimuli cause mast cell degranulation. Hemorrhagic shock is one such stressful stimulus which may cause mast cell degranulation and histamine release. Histamine may be involved in the pathophysiology of hemorrhage. It was reported that there are large amounts of histamine in the anterior and posterior lobes of the pituitary and the adjacent median eminence of the hypothalamus. Most of the histamine in the posterior pituitary is in mast cells. In addition, both vasoactive intestinal peptide (VIP) and histamine-containing neurons are available in the hypothalamus. It therefore seems reasonable to suppose that these three systems (i.e., mast cells, VIP-containing neurons, and histamine-containing neurons) may play an important role in the progression of hemorrhagic shock. 66 albino rats (200-250 g) of either sex were used. The presence of mast cells was examined by light microscopy. Hemorrhage caused mast cell degranulation in a correlation with the amount of blood loss. In all cases, the most intense degranulation was observed in the hypothalamus, especially the nucleus arcuatus, and in the subcutaneous tissue. The intensity of degranulation gradually decreased in the peripheral blood vessel, peritoneum and omentum, in this order. VIP prevented degranulation, but aprotinin and H1 and H2 receptor blockers did not.
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PMID:Mast cell degranulation in hemorrhagic shock in rats and the effects of vasoactive intestinal peptide, aprotinin and H1 and H2-receptor blockers on degranulation. 172 May 60

Circulating histamine-releasing factors have been identified in the serum and plasma of chronic-urticaria patients by in vivo skin testing and in vitro histamine release from heterologous mixed leukocytes. Quantitative mast cell studies of serum skin test biopsies and electron microscopy indicate that the serum factors release histamine by mast cell degranulation. Peripheral blood basophils and total cellular blood histamine are reduced in chronic-urticaria patients suggesting that the circulating serum factors cause sustained degranulation. Histamine-releasing activity has been identified by skin testing in ultrafiltered serum fractions less than 30 kDa and greater than 100 kDa. In vitro histamine-releasing activity was confined to ultrafiltered serum fractions greater than 100 kDa and was present in IgG purified from some chronic-urticaria sera by protein G affinity chromatography. The dose-response relationship and kinetics of histamine release in vitro were similar to those of anti-human IgE. 'Desensitisation' of basophils by prior incubation with anti-IgE in the absence of calcium and competitive inhibition studies with myeloma IgE serum indicated that histamine-releasing autoantibodies in chronic-urticaria sera and purified IgG have the properties of anti-IgE. Plasma exchange in 4 patients with active chronic urticaria refractory to antihistamine therapy showing in vivo and in vitro histamine-releasing activity was followed by temporary remission of disease activity in 2 of them. It is possible that chronic urticaria is an autoimmune disease.
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PMID:Histamine-releasing autoantibodies in chronic urticaria. 172 16

Besides its effects on tumour cells, tumour necrosis factor (TNF) also acts on a variety of other cells, thus enhancing inflammatory and immune processes. In view of the prominent role of the mast cell in such processes, the aim of the present study was to assess the effects of recombinant TNF-alpha on human mast cells. Mast cells from the infant foreskin obtained during circumcision were dispersed by an enzymatic technique using collagenase and hyaluronidase. Cells thus obtained were pooled, washed and separated by Percoll gradient centrifugation. Mast cells, with a purity of 70-90% were incubated for 60 min with 10(-11) to 10(-7) M rTNF-alpha. Histamine and tryptase levels were assessed in the cell supernatant by spectrofluorometry and radioimmunoassay (RIA) respectively. A concentration dependent release of histamine was observed, which reached a maximum of 11.5 +/- 2.2 nmol/10(6) cells at 10(-8) M rTNF. Release of tryptase was also concentration dependent and reached a maximum of 293 +/- 105 mU/10(6) cells (10(-8) rTNF). rTNF-alpha thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.
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PMID:Tumour necrosis factor stimulates human skin mast cells to release histamine and tryptase. 172 44

Murine interleukin 3 (IL-3) induces a strong, concomitant increase in histamine, interleukin 6 (IL-6), and interleukin 4 (IL-4) synthesis by progenitor-enriched bone marrow cell populations, whereas interleukin 2 (IL-2) or interferon-gamma (IFN-gamma) are undetectable. This phenomenon is observed between 4 and 12 h after exposure to the growth factor and attains maximal cytokine and histamine levels within 24 and 48 h, respectively. None of these mediators is produced by lymphoid populations such as lymph node cells or by granulocytes. Splenocytes secrete only low histamine and IL-6 levels, in accordance with the lower incidence of progenitors in the spleen, whereas total bone marrow cells generate substantial amounts of the three mediators even before enrichment. Histamine, IL-4-, and IL-6-producing cells copurify with immature cells and cannot be separated from each other throughout the sorting procedures used herein. They are concentrated in the low-density layers (buoyant density 1.069-1.086 g/cm3) of a discontinuous Ficoll gradient (less than 4% of the total bone marrow) together with the majority of hematopoietic progenitors (marrow-repopulating ability [MRA] cells, spleen colony-forming units [CFU-S] day-8 and day-12, granulocyte-macrophage colony-forming units [CFU-GM], and mast cell precursors). Their lightscatter characteristics are those of relatively large, granular cells. They do not belong to the most primitive stem cell subset (MRA and part of CFU-S day-12), but to a population with high mitochondrial activity identified by their important rhodamine retention (colony-forming unit cells [CFU-C], blast cells). In addition, we provide evidence that histamine, IL-4, and IL-6 do not depend on each other for their respective expression. Taken together, our data are consistent with the notion that in certain conditions, immature hematopoietic cells are a potent source of histamine and cytokines.
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PMID:Concomitant histamine, interleukin 4, and interleukin 6 production by hematopoietic progenitor subsets in response to interleukin 3. 183 45

Histamine exerts profound effects on the cardiovascular system during shock mediated by H1 and H2 receptors. The source of histamine is uncertain. It is our hypothesis that carnosine serves as a nonmast-cell reservoir for histidine, utilized for histamine synthesis during shock. We have shown that treatment of older rats with compound 48/80, a mast cell degranulator, produces age-dependent lethal stress, which is prevented by lodoxamide (LOD), a mast cell degranulation inhibitor, is exacerbated by H2 receptor blockade, and is accompanied by increased mobilization of myocardial carnosine to histidine and histamine. This study was designed to evaluate the effects of H1 and H2 blockers on carnosine mobilization to histamine during 48/80-induced shock in young rats. Fifty male SD rats (125 g) were divided into nine groups: saline; LOD; H1 blocker diphenhydramine (DPH); H2 blocker cimetidine (CIM); 48/80; LOD + 48/80; DPH + 48/80; CIM + 48/80; and DPH + CIM + 48/80. All rats were sacrificed 30 min after final injections and hearts were analyzed via HPLC. There was a reduction in myocardial carnosine (P less than or equal to 0.01) and histidine (P less than or equal to 0.001) and a simultaneous increase in histamine (P less than or equal to 0.01, P less than or equal to 0.001) in animals receiving 48/80 or CIM + 48/80, respectively, compared to controls or groups pretreated with LOD, DPH, or DPH + CIM. These results indicate that 48/80-induced shock increases mobilization of myocardial carnosine and histidine to histamine, which supports a role for carnosine as a nonmast-cell histamine source.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of H1 and H2 receptor blockers on mobilization of myocardial carnosine to histamine during compound 48/80-induced shock in young rats. 196 87

Although known for more than 80 years, histamine still remains a fascinating substance for allergy research. Histamine antagonists have been in clinical use since 1942. The classical H1-antagonists with sedative side-effects have been more or less replaced by newer non-sedating H1-antagonists; the role of H2-receptors in allergic diseases is still controversial. There, are however, increasing reports of beneficial effects of H2-antagonists, mostly in combination with H1-antagonists, in a variety of allergic and pseudoallergic conditions such as chronic urticaria, anaphylactoid reactions due to colloid volume substitutes, opioid analgesics and radiographic contrast media. The combined use of H1- and H2-antagonists might not only act as specific histamine antagonism but exert a mast cell stabilizing effect, as demonstrated in animal experiments and some clinical studies. Future research will show whether the combined use of H1- and H2-antagonists will become a routine therapeutic procedure in allergy therapy.
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PMID:H1- and H2-antagonists in allergic and pseudoallergic diseases. 197 7

The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.
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PMID:Role of neurotensin in radiation-induced hypothermia in rats. 202 92


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